This Program Project is a multidisciplinary effort dedicated to the study of Alzheimer's Disease (AD) and related disorders. It is built upon established investigative talents. This Project will consist of two components: A Clinical Core and Individual Research Projects. This Core will be dedicated to the recruitment and longitudinal assessment (1-year intervals) of 150- 175 demented, 50-60 depressed and 50-60 normal elderly individuals. They will receive extensive clinical and demographic assessment, neuropsychological, neurophysiological (spectral analysis EEG, computerized brain electrical activity mapping, cognitive and somatosensory evoked potentials), and neuroradiological (MRI) evaluations. Provision for neuropathological examination will be incorporated and all data analysis performed through this unit. Individual Research Projects will encompass many of the clinical, social and biological issues of dementing illness. They will interrelate through intellectual goals and the core patient population. These interactions will be further enhanced by the use of common patient data sets for all statistical analyses. Projects 1 and 2 will explore alternative methods for making a diagnosis and prognosis in AD by investigating peripheral cholinergic markers and activated regional cereberal blood flow. Project 3 will examine theraputic issues by investigating the usefulness of chronic oral physostigmine administration in AD. Project 4 will investigate basic biological mechanism, by exploring the role of tau, a protein associated with the paired- helical filament, in A.D. Finally, Project 5 will delve into social issues by exploring caregiver problems. The approach as outlined will provide an active interaction among investigators and thereby potentiate the likelihood that valuable new information on the neurobiological mechanisms of Alzheimer's Disease and related disorders will be acquired.